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1.
J Immunol ; 206(11): 2725-2739, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34021046

RESUMO

Innate lymphoid cells are central to the regulation of immunity at mucosal barrier sites, with group 2 innate lymphoid cells (ILC2s) being particularly important in type 2 immunity. In this study, we demonstrate that microRNA(miR)-142 plays a critical, cell-intrinsic role in the homeostasis and function of ILC2s. Mice deficient for miR-142 expression demonstrate an ILC2 progenitor-biased development in the bone marrow, and along with peripheral ILC2s at mucosal sites, these cells display a greatly altered phenotype based on surface marker expression. ILC2 proliferative and effector functions are severely dysfunctional following Nippostrongylus brasiliensis infection, revealing a critical role for miR-142 isoforms in ILC2-mediated immune responses. Mechanistically, Socs1 and Gfi1 expression are regulated by miR-142 isoforms in ILC2s, impacting ILC2 phenotypes as well as the proliferative and effector capacity of these cells. The identification of these novel pathways opens potential new avenues to modulate ILC2-dependent immune functions.


Assuntos
Linfócitos/imunologia , MicroRNAs/imunologia , Animais , Células HEK293 , Homeostase , Humanos , Imunidade Inata/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/genética
2.
Proc Natl Acad Sci U S A ; 112(51): 15725-30, 2015 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-26644587

RESUMO

All life demands the temporal and spatial control of essential biological functions. In bacteria, the recent discovery of coordinating elements provides a framework to begin to explain cell growth and division. Here we present the discovery of a supramolecular structure in the membrane of the coccal bacterium Staphylococcus aureus, which leads to the formation of a large-scale pattern across the entire cell body; this has been unveiled by studying the distribution of essential proteins involved in lipid metabolism (PlsY and CdsA). The organization is found to require MreD, which determines morphology in rod-shaped cells. The distribution of protein complexes can be explained as a spontaneous pattern formation arising from the competition between the energy cost of bending that they impose on the membrane, their entropy of mixing, and the geometric constraints in the system. Our results provide evidence for the existence of a self-organized and nonpercolating molecular scaffold involving MreD as an organizer for optimal cell function and growth based on the intrinsic self-assembling properties of biological molecules.


Assuntos
Membrana Celular/ultraestrutura , Staphylococcus aureus/ultraestrutura , Proteínas de Bactérias/análise , Entropia , Metabolismo dos Lipídeos , Staphylococcus aureus/química , Staphylococcus aureus/metabolismo
3.
Mol Microbiol ; 80(2): 542-55, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21401734

RESUMO

In Bacillus subtilis, EzrA is involved in preventing aberrant formation of FtsZ rings and has also been implicated in the localization cycle of Pbp1. We have identified the orthologue of EzrA in Staphylococcus aureus to be essential for growth and cell division in this organism. Phenotypic analyses following titration of EzrA levels in S. aureus have shown that the protein is required for peptidoglycan synthesis as well as for assembly of the divisome at the midcell and cytokinesis. Protein interaction studies revealed that EzrA forms a complex with both the cytoplasmic components of the division machinery and those with periplasmic domains, suggesting that EzrA may be a scaffold molecule permitting the assembly of the division complex and forming an interface between the cytoplasmic cytoskeletal element FtsZ and the peptidoglycan biosynthetic apparatus active in the periplasm.


Assuntos
Proteínas de Bactérias/metabolismo , Divisão Celular , Staphylococcus aureus/fisiologia , Proteínas de Bactérias/genética , Genes Essenciais , Peptidoglicano/metabolismo , Mapeamento de Interação de Proteínas , Staphylococcus aureus/genética
4.
Nat Cell Biol ; 23(12): 1224-1239, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34876685

RESUMO

Defective silencing of retrotransposable elements has been linked to inflammageing, cancer and autoimmune diseases. However, the underlying mechanisms are only partially understood. Here we implicate the histone H3.3 chaperone Daxx, a retrotransposable element repressor inactivated in myeloid leukaemia and other neoplasms, in protection from inflammatory disease. Loss of Daxx alters the chromatin landscape, H3.3 distribution and histone marks of haematopoietic progenitors, leading to engagement of a Pu.1-dependent transcriptional programme for myelopoiesis at the expense of B-cell differentiation. This causes neutrophilia and inflammation, predisposing mice to develop an autoinflammatory skin disease. While these molecular and phenotypic perturbations are in part reverted in animals lacking both Pu.1 and Daxx, haematopoietic progenitors in these mice show unique chromatin and transcriptome alterations, suggesting an interaction between these two pathways. Overall, our findings implicate retrotransposable element silencing in haematopoiesis and suggest a cross-talk between the H3.3 loading machinery and the pioneer transcription factor Pu.1.


Assuntos
Cromatina/patologia , Proteínas Correpressoras/genética , Transtornos Leucocíticos/congênito , Chaperonas Moleculares/genética , Mielopoese/genética , Proteínas Proto-Oncogênicas/metabolismo , Transativadores/metabolismo , Animais , Doenças Autoimunes/genética , Doenças Autoimunes/patologia , Linfócitos B/citologia , Linhagem Celular , Cromatina/genética , Células-Tronco Hematopoéticas/citologia , Histonas/metabolismo , Humanos , Inflamação/patologia , Transtornos Leucocíticos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Retroelementos/genética , Dermatopatias/genética , Dermatopatias/imunologia , Dermatopatias/patologia
5.
Water Environ Res ; 81(2): 165-72, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19323287

RESUMO

This article discusses key mechanisms involved in removing 1 mg/L Mn from synthetic wastewaters in constructed wetlands comprising water hyacinth (Eichhornia crassipes (Mart.) Solms) grown under different nutrient levels of 1-fold (28 mg/L and 7.7 mg/L of total nitrogen and total phosphorus, respectively), 2-fold, 1/4-fold, and 1/8-fold. A mass balance was carried out to evaluate the key removal mechanisms. Phytoremediation mainly due to phytoextraction substantially contributed to manganese removal. However, chemical precipitation was absent, suggesting that manganese has a higher solubility in the given average pH (6.2 to 7.1) conditions in constructed wetlands. Bacterial mediated immobilization mechanisms also did not contribute to manganese removal. Sediments constituted a minor sink to manganese, implying that manganese has a poor adsorption potential. Constructed wetlands comprising water hyacinth are effective at removing manganese from wastewaters despite the fact that the plants are grown under higher or lower nutrient conditions.


Assuntos
Eichhornia/metabolismo , Manganês/metabolismo , Poluentes Químicos da Água/metabolismo , Purificação da Água/métodos , Áreas Alagadas , Biodegradação Ambiental , Humanos , Resíduos Industriais
7.
J Environ Manage ; 87(3): 450-60, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-17383797

RESUMO

Severe contamination of water resources including groundwater with iron (Fe) due to various anthropogenic activities has been a major environmental problem in industrial areas of Sri Lanka. Hence, the use of the obnoxious weed, water hyacinth (Eichhornia crassipes (Mart.) Solms) in constructed wetlands (floating aquatic macrophyte-based plant treatment systems) to phytoremediate Fe-rich wastewaters seems to be an appealing option. Although several studies have documented that hyacinths are good metal-accumulating plants none of these studies have documented the ability of this plant grown under different nutrient conditions to remove heavy metals from wastewaters. This paper, therefore, reports the phytoremediation efficiencies of water hyacinth grown under different nutrient conditions for Fe-rich wastewaters in batch-type constructed wetlands. This study was conducted for 15 weeks after 1-week acclimatization by culturing young water hyacinth plants (average height of 20+/-2cm) in 590L capacity fiberglass tanks under different nutrient concentrations of 1-fold [28 and 7.7mg/L of total nitrogen (TN) and total phosphorous (TP), respectively], 2-fold, 1/2-fold, 1/4-fold and 1/8-fold with synthetic wastewaters containing 9.27Femg/L. Another set-up of hyacinths containing only Fe as a heavy metal but without any nutrients (i.e., 0-fold) was also studied. A mass balance was carried out to investigate the phytoremediation efficiencies and to determine the different mechanisms governing Fe removal from the wastewaters. Fe removal was largely due to phytoremediation mainly through the process of rhizofiltration and chemical precipitation of Fe2O3 and FeOH3 followed by flocculation and sedimentation. However, chemical precipitation was more significant especially during the first 3 weeks of the study. Plants grown in the 0-fold set-up showed the highest phytoremediation efficiency of 47% during optimum growth at the 6th week with a highest accumulation of 6707Femg/kg dry weight. Active effluxing of Fe back to the wastewater at intermittent periods and with time was a key mechanism of avoiding Fe phytotoxicity in water hyacinth cultured in all set-ups. Our study elucidated that water hyacinth grown under nutrient-poor conditions are ideal to remove Fe from wastewaters with a hydraulic retention time of approximately 6 weeks.


Assuntos
Eichhornia/metabolismo , Recuperação e Remediação Ambiental/métodos , Ferro/isolamento & purificação , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/isolamento & purificação , Áreas Alagadas , Biodegradação Ambiental , Eichhornia/crescimento & desenvolvimento , Resíduos Industriais , Nitrogênio/metabolismo , Fósforo/metabolismo , Fatores de Tempo
8.
Artigo em Inglês | MEDLINE | ID: mdl-17182390

RESUMO

This article reports the phytoremediation efficiencies of water hyacinth (Eichhornia crassipes (Mart.) Solms) grown under different nutritional conditions for Al rich wastewaters in batch type constructed wetlands (floating aquatic macrophyte-based plant treatment systems). This study was conducted for 15 weeks after 1 week acclimatization by culturing young water hyacinth (average height of 20 +/- 2 cm) in 590 L capacity fiberglass tanks under different nutrient concentrations of 2-fold [56 and 15.4 mg/L of total nitrogen (TN) and total phosphorous (TP), respectively], 1-fold, 1/2-fold, 1/4-fold and 1/8-fold with synthetic wastewaters containing 5.62 Al mg/L. A control set-up of hyacinths comprising only Al with no nutrients was also studied. A mass balance was carried out to investigate the phytoremediation efficiencies and to identify the different Al removal mechanisms from the wastewaters. Chemical precipitation of Al(OH)3 was a dominant contribution to Al removal at the beginning of the study, whereas adsorption of Al3+ to sediments was observed to be a predominant Al removal mechanism as the study progressed. Phytoremediation mainly due to rhizofiltration was also an important mechanism of Al removal especially during the first 4 weeks of the study in almost all the set-ups. However, chemical precipitation and sediment adsorption of Al3+ was a dominant contribution to Al removal in comparison with phytoremediation. Plants cultured in the control set-up showed the highest phytoremediation efficiency of 63% during the period of the 4th week. A similar scenario was evident in the 1/8-fold set-up. Hence we conclude that water hyacinth grown under lower nutritional conditions are more ideal to commence a batch type constructed wetland treating Al rich wastewaters with a hydraulic retention time of approximately 4 weeks, after which a complete harvesting is recommended.


Assuntos
Alumínio/metabolismo , Eichhornia/metabolismo , Áreas Alagadas , Alumínio/análise , Alumínio/isolamento & purificação , Biodegradação Ambiental , Eichhornia/crescimento & desenvolvimento , Recuperação e Remediação Ambiental/métodos , Fatores de Tempo , Eliminação de Resíduos Líquidos/métodos , Poluição Química da Água/análise , Poluição Química da Água/prevenção & controle
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